Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis
- University of Bonn, Germany
- Universitätsklinikum Erlangen, Germany
- German Center for Neurodegenerative Diseases, Germany
Abstract
During embryogenesis, the fetal liver becomes the main hematopoietic organ, where stem and progenitor cells as well as immature and mature immune cells form an intricate cellular network. Hematopoietic stem cells (HSCs) reside in a specialized niche, which is essential for their proliferation and differentiation. However, the cellular and molecular determinants contributing to this fetal HSC niche remain largely unknown. Macrophages are the first differentiated hematopoietic cells found in the developing liver, where they are important for fetal erythropoiesis by promoting erythrocyte maturation and phagocytosing expelled nuclei. Yet, whether macrophages play a role in fetal hematopoiesis beyond serving as a niche for maturing erythroblasts remains elusive. Here, we investigate the heterogeneity of macrophage populations in the murine fetal liver to define their specific roles during hematopoiesis. Using a single-cell omics approach combined with spatial proteomics and genetic fate-mapping models, we found that fetal liver macrophages cluster into distinct yolk sac-derived subpopulations and that long-term HSCs are interacting preferentially with one of the macrophage subpopulations. Fetal livers lacking macrophages show a delay in erythropoiesis and have an increased number of granulocytes, which can be attributed to transcriptional reprogramming and altered differentiation potential of long-term HSCs. Together, our data provide a detailed map of fetal liver macrophage subpopulations and implicate macrophages as part of the fetal HSC niche.
Data availability
RNA-seq data from bulk and single-cell experiments are available under GEO accession number GSE225444. Source data for CODEX pictures (raw .tiff files) and analyses are available as pyramidal file at Dryad (Mass, Elvira (2023), Source Data Kayvanjoo et al., Dryad, Dataset, https://doi.org/10.5061/dryad.fn2z34v00). Due to size restrictions, the original CODEX .czi files could not be uploaded, but will be made available without restrictions after contacting the corresponding author.
-
Source Data Kayvanjoo et al. CODEX of fetal livers at E14.5Dryad Digital Repository, doi:10.5061/dryad.fn2z34v00.
Article and author information
Author details
Amir Hossein Kayvanjoo
Funding
Deutsche Forschungsgemeinschaft (EXC2151-390873048)
- Joachim L Schultze
- Eva Kiermaier
- Marc Beyer
- Andreas Schlitzer
- Elvira Mass
Deutsche Forschungsgemeinschaft (505539112)
- Stefan Uderhardt
Hightech Agenda Bavaria
- Stefan Uderhardt
Horizon 2020 Framework Programme (101039438)
- Stefan Uderhardt
Deutsche Forschungsgemeinschaft (GRK2168)
- Katharina Mauel
- Elvira Mass
Deutsche Forschungsgemeinschaft (GRK1873/2)
- Elvira Mass
Deutsche Forschungsgemeinschaft (SFB1454)
- Joachim L Schultze
- Marc Beyer
- Andreas Schlitzer
- Elvira Mass
Deutsche Forschungsgemeinschaft (FOR5547 - Project-ID 503306912)
- Elvira Mass
Boehringer Ingelheim Stiftung
- Katharina Mauel
Horizon 2020 Framework Programme (851257)
- Elvira Mass
Deutsche Forschungsgemeinschaft (448121430)
- Stefan Uderhardt
Deutsche Forschungsgemeinschaft (405969122)
- Stefan Uderhardt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations of the LANUV and Veterinary Office of the City of Bonn. All of the animals were handled according to approved institutional animal care at the LIMES GRC. The protocol was approved by the LANUV (Permit Number: 2018.A056).
Copyright
© 2024, Kayvanjoo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,398
- views
-
- 351
- downloads
-
- 12
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Fetal liver macrophages contribute to the hematopoietic stem cell niche by controlling granulopoiesis
eLife 13:e86493.
https://doi.org/10.7554/eLife.86493
Further reading
-
- Cell Biology
- Developmental Biology
A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.
-
- Developmental Biology
The intricate coordination of the neural network in planarian growth and regeneration has remained largely unrevealed, partly due to the challenges of imaging the CNS in three dimensions (3D) with high resolution and within a reasonable timeframe. To address this gap in systematic imaging of the CNS in planarians, we adopted high-resolution, nanoscale imaging by combining tissue expansion and tiling light-sheet microscopy, achieving up to fourfold linear expansion. Using an automatic 3D cell segmentation pipeline, we quantitatively profiled neurons and muscle fibers at the single-cell level in over 400 wild-type planarians during homeostasis and regeneration. We validated previous observations of neuronal cell number changes and muscle fiber distribution. We found that the increase in neuron cell number tends to lag behind the rapid expansion of somatic cells during the later phase of homeostasis. By imaging the planarian with up to 120 nm resolution, we also observed distinct muscle distribution patterns at the anterior and posterior poles. Furthermore, we investigated the effects of β-catenin-1 RNAi on muscle fiber distribution at the posterior pole, consistent with changes in anterior-posterior polarity. The glial cells were observed to be close in contact with dorsal-ventral muscle fibers. Finally, we observed disruptions in neural-muscular networks in inr-1 RNAi planarians. These findings provide insights into the detailed structure and potential functions of the neural-muscular system in planarians and highlight the accessibility of our imaging tool in unraveling the biological functions underlying their diverse phenotypes and behaviors.
